Endogenous BK stimulates ischemically sensitive abdominal visceral C fiber afferents through kinin B2 receptors
Pan, H.L.; Stahl, G.L.; Rendig, S.V.; Carretero, O.A.; Longhurst, J.C.
American Journal of Physiology 267(6 Pt 2): H2398-H2406
1994
ISSN/ISBN: 0002-9513 PMID: 7810739 Document Number: 433604
Abdominal ischemia and reperfusion reflexly activate the cardiovascular system. In the present study, we evaluated the role of endogenously produced bradykinin (BK) in the stimulation of ischemically sensitive visceral afferents. Single-unit activity of abdominal visceral C fiber afferents was recorded from the right thoracic sympathetic chain of anesthetized cats during 5 min of abdominal ischemia. Abdominal ischemia increased the portal venous plasma BK level from 49 +- 10 to 188 +- 66 pg/ml (P lt 0.05). Injection of BK (1 mu-g/kg ia) into the descending aorta significantly increased impulse activity (0.88 +- 0.16 impulses/s) of 10 C fibers, whereas a kinin B-1-receptor agonist, des-Arg-9-BK (1 mu-g/kg), did not alter the discharge rate. Inhibition of kininase II activity with captopril (4 mg/kg iv) potentiated impulse activity of 14 ischemically sensitive C fibers (0.44 +- 0.09 vs. precaptopril, 0.33 +- 0.08 impulses/s; P lt 0.05). In addition, a kinin B-2-receptor antagonist (NPC-17731; 40 mu-g/kg iv) attenuated activity of afferents during ischemia (0.39 +- 0.08 vs. pre-NPC-17731, 0.72 +- 0.13 impulses/s; P lt 0.05) and eliminated the response of 10 C fibers to BK. Another kinin B-2-receptor antagonist, Hoe-140 (30 mu-g/kg iv), had similar inhibitory effects on six other ischemically sensitive C fibers. In 15 separate cats treated with aspirin (50 mg/kg iv), Hoe-140 (30 mu-g/kg iv) attenuated impulse activity of only 3 of 16 ischemically sensitive C fibers. These data suggest that BK produced during abdominal ischemia contributes to the stimulation of ischemically sensitive visceral C fiber afferents through kinin B-2 receptors. Furthermore, the data indicate that for most ischemically sensitive C fibers (81%), BK activates the cyclooxygenase system to augment afferent activity during abdominal ischemia.